Abstract: Methods and devices for the detection and identification in a sample of one or more target molecules which bind to nucleic acid probe molecules are provided. The method includes contacting the sample with a surface that is coated with one or more gradients of nucleic acid or nucleic acid analog probe molecules that bind target molecules in the sample. Gradients are formed by varying a physical, structural or functional property of the probes on the surface; for example, the density of probe molecules bound to the surface. The coating layer or immobilization layer in which the gradient is formed is preferably continuous Determination of the location, speed and/or extent of hybridisation of a nucleic acid on a gradient surface is useful to identify target molecules bound to probes and/or to quantitatively measure the amount of the target in a sample.

Abstract: The present invention is directed to a PCR-based method of cycle sequencing DNA and other polynucleotide sequences having high CG content and regions of high GC content, and includes for example DNA strands with a high Cytosine and/or Guanosine content and repeated motifs such as CCT repeats.

Abstract: The invention provides iterative methods of analyzing a target nucleic acid that represents a variant of a reference nucleic acid. An array of probes is designed to be complementary to an estimated sequence of a target nucleic acid. The array of probes is then hybridized to the target nucleic acid. The target sequence is reestimated from hybridization pattern of the array to the target nucleic acid. A further array of probes is then designed to be complementary to the reestimated sequence, and this array is used to obtain a further reestimate of the sequence of the target nucleic acid. By performing iterative cycles of array design and target sequence estimation, the estimated sequence of the target converges with the true sequence.

Abstract: This invention uses a receptor molecule such as an antibody etc immobilized to a chip for a solid phase, and a sensor such as a pH electrode or an oxygen electrode or a glucose electrode for a search device. After immobilizing specific living cells by a bio-specific recognition reaction (a special immunity bond reaction) and washing the solid phase chip, one can measure the change of pH or oxygen consumption or glucose consumption from the metabolism of the specific living cells in substrate solution. This makes it possible to measure the activity and quantity of living cells specifically, accurately and quickly.

Abstract: A method, apparatus, and computer program products for fabricating multiple chemical arrays on a substrate, each array having multiple rows of feature locations with arrays of different sets being arranged in a sideways orientation with respect to the rows. The method includes dispensing drops from a drop dispensing head onto the substrate while maintaining a gap between the head and substrate and moving them relative to one another along a path so as to fabricate the arrays. The path for the relative moving includes moving the head in a direction along the rows of a first array set then moving the head in an opposite direction along the rows of a second array set. This pattern is repeated with the second array set of an earlier cycle being the first array set of a later cycle.

Abstract: The present invention provides a simple, cost-effective, universal method for determining and/or quantifying differences in nucleic acid levels between two or more test mixtures without prior knowledge of the sequence of the nucleic acids of interest. The method involves providing a universal microarray containing a plurality of spots, where each spot contains a plurality, or pool, of different oligonucleotide probes having at least three distinct portions: a universal sequence portion, a short central variable “wobble” sequence portion, and a unique sequence portion. A set of probes is synthesized such that the universal sequence portion is the same for every probe, and all possible permutations of the wobble sequence and unique sequence portions are represented in approximately equal concentrations in the set.

Abstract: Apparatus and methods for monitoring, analyzing, and/or discriminating molecular species, preferably a biomolecule, within a medium using a multisensor array (MSA) and multivariate processing. Biological compounds such as nucleotides and polynucleotides can be detected and analyzed. A reaction process such as an accumulation cycle of nucleic acids can be monitored, analyzed, and controlled using a multisensor array (MSA) and multivariate processing. Monitoring a biomolecule includes interrogating the medium, and preferably its gas phase, by coupling a sensor responsive to any changes of the medium and or biomolecule and its secondary products when, for example, an amplification reaction is proceeded. It is also a scope of the present invention to use direct detection and monitoring of biomolecular reactions in real-time without radioactive or fluorescent labeling. A preferred application is real-time polymerase chain reaction (PCR) detection.

Abstract: Provided is a method for sequencing DNA, which comprises: (a) obtaining a target DNA population comprising one or more single-stranded DNAs to be sequenced, each of which is present in a unique amount and bears a primer to provide a double-stranded portion of the DNA for ligation thereto; (b) contacting the DNA population with an array of hybridisation probes, each probe comprising a label cleavably attached to a known base sequence of predetermined length, the array containing all possible base sequences of that predetermined length; (c) removing all unligated probes; followed by the steps of: (d) cleaving the ligated probes to release each label; (e) recording the quantity of each label; and (f) activating the extended double-stranded portion to enable ligation thereto; wherein (g) steps (b) to (f) are repeated in a cycle for a sufficient number of times to determine the sequence of the or each single-stranded DNA by determining the sequence of release of each label.

Abstract: The invention provides an apparatus and method for determining a signal produced by a micro array device. The apparatus provides an unstructured probe and structured probe. The unstructured probe binds to a target and provides a first signal that can be compared to a second signal produced by a structured probe. A more accurate level of intensity of the first signal can be determined by comparing to the second signal produced by the structured probe. A method for determining a more accurate level of signal intensity produced from the unstructured probes bound to the target is also disclosed.

Abstract: Methods are disclosed for synthesizing a plurality of compounds on the surface of supports. The synthesis comprises a series of cycles of steps in which reagents for conducting the synthesis are deposited on the surface of the support to form the chemical compounds. At least one physical parameter of the deposition varies between cycles The method comprises conducting the synthesis in at least two sets of cycles, arbitrarily designated as a first set and a second set. Each cycle comprises at least one step of depositing reagents on a surface by means of droplet dispensing elements that traverse the surface of the support. At least one, and desirably all, of the following deposition parameters are employed as indicated: The number of times of repetition for a step of depositing reagents in at least one cycle of the second set is less than the number of times of repetition for a corresponding step in at least one cycle of the first set.

Abstract: A method for characterizing DNA, which comprises: (i) providing a population of DNA fragments, each fragment having cleavably attached thereto a mass label for identifying a feature of that fragment; (ii) separating the fragments on the basis of their length; (iii) cleaving each fragment in a mass spectrometer to release its mass label; and (iv) determining each mass label by mass spectrometry to relate the feature of each fragment to the length of the fragment.

Abstract: Long oligonucleotide arrays, as well as methods for their preparation and use in hybridization assays, are provided. The subject arrays are characterized in that at least a portion of the probes of the array, and usually all of the probes of the array, are long oligonucleotides, e.g. oligonucleotides having a length of from about 50 to 120 nt. Each long oligonucleotide probe on the array is preferably chosen to exhibit substantially the same high target binding efficiency and substantially the same low non-specific binding under conditions in which the array is employed. The subject arrays find use in a number of different applications, e.g. differential gene expression analysis.

Abstract: The invention relates to compositions and methods for decoding microsphere array sensors.

Abstract: Methods and apparatus for delivering a plurality of different biological materials onto discrete locations on a receiving surface, as for example to fabricate an array of different biological materials. The apparatus and methods may include a plurality of orifices in an orifice member, at least six delivery chambers each in fluid conducting relationship with at least one of the orifices, a plurality of reservoirs each in fluid communication with at least one of the delivery chambers, means associated with each orifice for propelling fluid through the associated orifice from the delivery chamber that is in fluid conducting relationship with the orifice, and a vent for commonly venting at least two of the reservoirs. In some embodiments the chambers and reservoirs are loaded with fluids containing selected biomolecules by drawing the selected fluids into the chambers through the orifices; in other embodiments the fluids are introduced into the reservoirs.

Abstract: A composite material sheet which is composed of partitions two-dimensionally extending on a sheet plane to form on the sheet plane plural fine sections surrounded by the partitions and porous material portions each of which is placed in the fine section, or a simple porous sheet is employed for autoradiographic analysis of substances originating from living body or its analogues in combination with a stimulable phosphor sheet which is composed of a support and fine stimulable phosphor layers distributed on the support in such manner that each stimulable phosphor layer takes a position corresponding to each fine section of the composite material sheet or a position of the porous sheet in which probe molecules are spotted.

Abstract: The present invention is a dedicated apparatus for the formation of array that includes one or more deposition domains comprised of one or more deposition materials. The present invention may include an X, Y controller, an X, Y translation stage, a loading substrate, a deposition substrate, a Z controller, and a deposition probe. A computer controls all of the relative positions of each of the components. Furthermore, the present invention utilizes a humidity control system to create a capillary bridge between the probe and the substrate for transferring the deposition material between the loading substrate, the deposition probe, and the deposition substrate.

Abstract: Methods are described for the identification and preparation of nucleic acid ligands to tenascin-C. Included in the invention are specific RNA ligands to tenascin-C identified by the SELEX method. Further included in the invention are methods for detecting the presence of a disease condition in a biological tissue in which tenascin-C is expressed.

Abstract: A planar, rigid substrate made from a porous, inorganic material coated with cationic polymer molecules for attachment of an array of biomolecules, such as DNA, RNA, oligonucleotides, peptides, and proteins. The substrate has a top surface with about at least 200 to about 200,000 times greater surface area than that of a comparable, non-porous substrate. The cationic polymer molecules are anchored on the top surface and in the pores of the porous material. In high-density applications, an array of polynucleotides of a known, predetermined sequence is attached to this cationic polymer layer, such that each of the polynucleotide is attached to a different localized area on the top surface. The top surface has a surface area for attaching biomolecules of approximately 387,500 cm2/cm2 of area (˜7.5 million cm2/1×3 inch piece of substrate). Each pore of the plurality of pores in the top surface of the substrate has a pore radius of between about 40 ? to about 75 ?.

Abstract: The present invention relates to an oligonucleotide having a novel structure and a method of synthesizing nucleic acid by using the same as a primer. This oligonucleotide is provided at the 5?-side of the primer with a nucleotide sequence substantially the same as a region synthesized with this primer as the origin of synthesis. The present invention realizes synthesis of nucleic acid based on an isothermal reaction with a simple constitution of reagents. Further, the present invention provides a method of synthesizing highly specific nucleic acid on the basis of this method of synthesizing nucleic acid.

Abstract: A method for fabricating matrices of addressed ligands on a carrier. In the method, an element is used such as a reservoir filled with ligand and containing an electrode to deposit and electrochemically fix the ligand to the conductive carrier. The ligand may be an oligonucleotide or a peptide, and fixing may be obtained by electrocopolymerisation of this oligonucleotide or peptide carrying a pyrrole group at 5? with pyrrole.